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Diabetes, Obesity & Metabolism Aug 2023To conduct a systematic review of observational studies to explore the real-world kidney benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in a large and... (Meta-Analysis)
Meta-Analysis
AIM
To conduct a systematic review of observational studies to explore the real-world kidney benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in a large and diverse population of adults with type 2 diabetes (T2D).
MATERIALS AND METHODS
We searched MEDLINE, EMBASE and Web of Science for observational studies that investigated kidney disease progression in adults with T2D treated with SGLT2 inhibitors compared to other glucose-lowering therapies. Studies published from database inception to July 2022 were independently reviewed by two authors and evaluated using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. A random-effects meta-analysis was performed on studies with comparable outcome data, reported as hazard ratios (HRs) with 95% confidence intervals (CIs).
RESULTS
We identified 34 studies performed across 15 countries with a total population of 1 494 373 for inclusion. In the meta-analysis of 20 studies, SGLT2 inhibitors were associated with a 46% lower risk of kidney failure events compared with other glucose-lowering drugs (HR 0.54, 95% CI 0.47-0.63). This finding was consistent across multiple sensitivity analyses and was independent of baseline estimated glomerular filtration rate (eGFR) or albuminuria status. SGLT2 inhibitors were associated with a lower risk of kidney failure when compared with dipeptidyl peptidase-4 inhibitors and a combination of other glucose-lowering drug classes (HR 0.50, 95% CI 0.38-0.67 and HR 0.51, 95% CI 0.44-0.59, respectively). However, when compared to glucagon-like peptide 1 receptor agonists there was no statistically significant difference in the risk of kidney failure (HR 0.93, 95% CI 0.80-1.09).
CONCLUSIONS
The reno-protective benefits of SGLT2 inhibitors apply to a broad population of adults with T2D treated in routine clinical practice, including those at lower risk of kidney events with normal eGFR and without albuminuria. These findings support the early use of SGLT2 inhibitors in T2D for preservation of kidney health.
Topics: Humans; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Albuminuria; Kidney; Renal Insufficiency; Glucose; Sodium; Hypoglycemic Agents
PubMed: 37202870
DOI: 10.1111/dom.15111 -
Frontiers in Pharmacology 2022Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors play a key role in the treatment of type 2 diabetes mellitus. This... (Review)
Review
Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors play a key role in the treatment of type 2 diabetes mellitus. This meta-analysis aims to evaluate the efficacy and safety of their combination, emphatically focusing on the effects of treatment duration and add-on drugs. Seven databases were searched until June 2021 for randomized controlled trials with a duration of at least 12 weeks, evaluating the effects of combination therapy with glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors. A total of eight eligible articles were included, pooling data retrieved from 1895 patients with type 2 diabetes mellitus. Compared to monotherapy, combination therapy resulted in a greater reduction in glycated haemoglobin (HbA1c), body weight, fasting plasma glucose (FPG), 2 h postprandial glucose (2 h PG), systolic blood pressure (SBP), body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C). The decrease in HbA1c, body weight and FPG was maintained for more than 1 year, but these effects gradually regressed over time. The risk for hypoglycaemia was significantly increased with combination therapy. In addition, drug discontinuation, diarrhoea, injection-site-related events, nausea, vomiting and genital infections were more likely to occur in combination therapy. Glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor combination therapy showed superior effects on reducing HbA1c, body weight, FPG, 2 h PG, SBP, BMI and LDL-C, without major safety issues, when compared with monotherapy in patients with type 2 diabetes mellitus.
PubMed: 35185588
DOI: 10.3389/fphar.2022.838277 -
Diabetes, Obesity & Metabolism May 2024Using a systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials (CVOTs) of newer glucose-lowering agents [sodium-glucose cotransporter-2... (Meta-Analysis)
Meta-Analysis
Glycaemic control and macrovascular and microvascular outcomes in type 2 diabetes: Systematic review and meta-analysis of cardiovascular outcome trials of novel glucose-lowering agents.
AIM
Using a systematic review and meta-analysis of placebo-controlled cardiovascular outcome trials (CVOTs) of newer glucose-lowering agents [sodium-glucose cotransporter-2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is)] in type 2 diabetes (T2D), we aimed to determine the macrovascular and microvascular outcomes of these agents and clarify the relationships between glycated haemoglobin (HbA1c) reduction and risk of these outcomes.
MATERIALS AND METHODS
Randomized controlled trials were identified from MEDLINE, Embase and the Cochrane Library until September 2023. Study-specific hazard ratios with 95% confidence intervals (CIs) were pooled, and meta-regression was used to assess the relationships between outcomes and between trial arm HbA1c reductions.
RESULTS
Twenty unique CVOTs (six SGLT-2is, nine GLP-1RAs, five DPP-4is), based on 169 513 participants with T2D, were eligible. Comparing SGLT-2is, GLP-1RAs and DPP-4is with placebo, the hazard ratios (95% CIs) for 3-point major adverse cardiovascular events were 0.88 (0.82-0.94), 0.85 (0.79-0.92) and 1.00 (0.94-1.06), respectively. SGLT-2is and GLP-1RAs consistently reduced the risk of several macrovascular and microvascular complications, particularly kidney events. DPP-4is showed no macrovascular benefits. There was potential evidence of an inverse linear relationship between HbA1c reduction and 3-point major adverse cardiovascular event risk (estimated risk per 1% reduction in HbA1c: 0.84, 95% CI 0.67-1.06; p = .14; R = 14.2%), which was driven by the component of non-fatal stroke (R = 100.0%; p = .094). There were non-significant inverse linear relationships between HbA1c reduction and the risk of several vascular outcomes.
CONCLUSIONS
SGLT-2is and GLP-1RAs showed consistent risk reductions in macrovascular and microvascular outcomes. The vascular benefits of SGLT-2is and GLP-1RAs in patients with T2D extend beyond mere glycaemic control.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; Glucose; Glycated Hemoglobin; Glycemic Control; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor
PubMed: 38379094
DOI: 10.1111/dom.15500 -
High Blood Pressure & Cardiovascular... Nov 2021Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in... (Meta-Analysis)
Meta-Analysis
Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients with Type 2 Diabetes Without Baseline Metformin: A Systematic Review and Update Meta-analysis.
INTRODUCTION
Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy.
AIM
To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naïve patients with type 2 diabetes.
METHODS
A systematic review and meta-analysis of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes population was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoints were cardiovascular death and all-cause mortality. A meta-analysis of time-to-event outcomes was performed. This meta-analysis was registered in PROSPERO (CRD42021260040) RESULTS: Seven trials, including 11510 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.86, 95% confidence interval: 0.79-0.94; I: 0%). The secondary endpoints analysis showed a non-significant reduction in all-cause mortality (HR: 0.86, 95% confidence interval: 0.73-1.00 I: 0%) and cardiovascular mortality (HR: 0.81, 95% confidence interval: 0.63-1.05; I: 0%).
CONCLUSIONS
In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results support the fact that when a GLP-1RAs is administered, the benefit on cardiovascular outcomes is independent of the use of metformin.
Topics: Cardiotonic Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Metformin
PubMed: 34705249
DOI: 10.1007/s40292-021-00479-1 -
Diabetic Medicine : a Journal of the... Mar 2022To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes. (Comparative Study)
Comparative Study Meta-Analysis
Comparative effectiveness of cardiovascular, renal and safety outcomes of second-line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta-analysis of randomised controlled trials.
AIMS
To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes.
METHODS
MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta-analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322).
RESULTS
We included 38 trials from seven classes of glucose-lowering therapies. Both sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3-point major adverse cardiovascular events, 3P-MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84-0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83-0.93; NNT, 50]), cardiovascular death, all-cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP-4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty).
CONCLUSIONS
SGLT2i and GLP1RA were associated with lower risk for different cardiorenal end points, when used as an adjunct to metformin in people with type 2 diabetes. Additionally, SGLT2i demonstrated benefits in reducing risk for surrogate end points in kidney disease progression. Safety outcomes differ among the available pharmacotherapies.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Insulin; Kidney Diseases; Metformin; Network Meta-Analysis; Pancreatitis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Thiazolidinediones
PubMed: 34962662
DOI: 10.1111/dme.14780 -
PloS One 2021Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by... (Meta-Analysis)
Meta-Analysis
Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis.
BACKGROUND AND AIMS
Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large-scale randomized controlled studies (RCTs) and systematic reviews of RCTs, but exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we analyzed the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM).
METHODS
We did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was MACE and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region.
RESULTS
Fourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P<0.001) and ACM (OR, 0.53; 95% CI 0.49,0.57, P<0.001) compared to other glucose lowering drugs (oGLD). Compared with oGLD, SGLT-2i had significantly lowered the risk of HHF (OR, 0.56; 95% CI 0.46,0.68, P<0.001), MI (OR, 0.77; 95% CI 0.73,0.81, P<0.001), stroke (OR, 0.75; 95% CI 0.72,0.78, P<0.001), CVM (OR, 0.58; 95% CI 0.49,0.69, P<0.001) and HF (OR, 0.56; 95% CI 0.48,0.67, P<0.001), but there was no benefit from UA or AF. SGLT-2i significantly reduced the risk of severe hypoglycemia (OR, 0.78; 95% CI 0.69,0.90, P<0.001) and lower limb amputation (OR, 0.83; 95% CI 0.71,0.98, P<0.001), but it may increase the risk of diabetic ketoacidosis. Subgroup analysis showed SGLT-2i reduced the risk of MACE, ACM, HHF, MI, stroke, CVM and HF with a similar benefit regardless of the incidence of CVD was (20-30)% or < 15%, (15-30)% or <15% have been treated with GLP-1 receptor agonists (GLP-1RA), >80% or <70% have been treated with statins or both GLP-1RA and statins. SGLT-2i reduced the risk of ACM in low-risk population (P<0.001). No inconsistencies were found when stratification was performed at 1 or (3-4) years of follow-up except for BKA followed up for 1 year. SGLT-2i showed similar cardiovascular benefits in the Nordic countries, Asia and the United States.
CONCLUSIONS
The predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i has robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin. SGLT-2i does not increase the risk of severe hypoglycemia and lower limb amputation.
Topics: Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Glucose; Heart Failure; Humans; Hypoglycemic Agents; Metformin; Myocardial Infarction; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33606705
DOI: 10.1371/journal.pone.0244689 -
Diabetes, Obesity & Metabolism Oct 2020To assess the efficacy and safety of combination therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) and a sodium-glucose co-transporter-2 inhibitor... (Meta-Analysis)
Meta-Analysis
Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta-analysis.
AIM
To assess the efficacy and safety of combination therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) and a sodium-glucose co-transporter-2 inhibitor (SGLT2i) in patients with type 2 diabetes.
METHODS
We searched Medline, Embase, the Cochrane Library and grey literature sources up to 2 December 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP-1RA and SGLT2i, either as co-initiation therapy or as add-on to each other, against placebo or an active comparator. The primary outcome was change in HbA . Secondary outcomes included change in body weight, blood pressure and estimated glomerular filtration rate, and incidence of severe hypoglycaemia, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta-analyses.
RESULTS
Seven trials (1913 patients) were eligible. Compared with GLP-1RA, GLP-1RA/SGLT2i combination therapy was associated with a greater reduction in HbA1c (weighted mean difference -0.61%, 95% CI -1.09% to -0.14%, four studies), body weight (-2.59 kg, -3.68 to -1.51 kg, three studies) and systolic blood pressure (-4.13 mmHg, -7.28 to -0.99 mmHg, four studies). Compared with SGLT2i, GLP-1RA/SGLT2i combination therapy reduced HbA1c (-0.85%, -1.19% to -0.52%, six studies) and systolic blood pressure (-2.66 mmHg, -5.26 to -0.06 mmHg, six studies), but not body weight (-1.46 kg, -2.94 to 0.03 kg, five studies). After excluding data for one trial that had a considerably longer duration than the remaining studies, body weight was also reduced versus SGLT2i (-1.79 kg, -2.99 to -0.59 kg, five studies). Combination therapy did not increase the incidence of severe hypoglycaemia. Data for mortality and cardiovascular outcomes were scarce.
CONCLUSIONS
GLP-1RA/SGLT2i combination therapy seems to reduce HbA , body weight and systolic blood pressure without increasing the risk of severe hypoglycaemia compared with either GLP-1RA or SGLT2i. No conclusions can be made regarding long-term effectiveness or the effect on cardiovascular outcomes.
Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 32476254
DOI: 10.1111/dom.14108 -
Diabetes Research and Clinical Practice Dec 2019Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type... (Meta-Analysis)
Meta-Analysis
Glycemic efficacy and safety of glucagon-like peptide-1 receptor agonist on top of sodium-glucose co-transporter-2 inhibitor treatment compared to sodium-glucose co-transporter-2 inhibitor alone: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). The purpose of this meta-analysis was to provide precise effect estimates regarding the safety and efficacy of the addition of a GLP-1RA on top of SGLT-2i treatment.
RESEARCH DESIGN AND METHODS
PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration ≥ 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM. We also used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the credibility of our summary estimates.
RESULTS
We identified three eligible RCTs, pooling data retrieved from 1,042 patients with T2DM in total. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in significant decrease in HbA1c by 0.91% (95% CI; -1.41 to -0.42) [GRADE: moderate], in body weight by 1.95 kg (95% CI; -3.83 to -0.07) [GRADE: moderate], in fasting plasma glucose by 1.53 mmol/L (95% CI; -2.17 to -0.88) [GRADE: moderate] and in systolic blood pressure levels by 3.64 mm Hg (95% CI -6.24 to -1.03). No significant effects on lipid profile and diastolic blood pressure were demonstrated. A significant increase in the risk for any hypoglycemia (RR: 2.62, 95% CI; 1.15-5.96, I = 33%) [GRADE: moderate] and for nausea (RR: 3.21, 95% CI; 1.36-7.54, I = 63%) [GRADE: moderate] and a non-significant increase in the risk for diarrhoea (RR: 1.64, 95% CI; 0.98-2.75, I = 0%) [GRADE: low] were documented. No other safety issues were identified.
CONCLUSIONS
This meta-analysis suggests that a GLP-1RA/SGLT-2i combination, if tolerated, exerts significant beneficial effects on glycemic control and body weight loss, however increasing the risk for any hypoglycemia and gastrointestinal adverse events.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31733280
DOI: 10.1016/j.diabres.2019.107927 -
Diabetes, Obesity & Metabolism Aug 2022Most trials leading to the approval of glucagon-like peptide receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) were primarily...
Non-inferiority and clinical superiority of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors: Systematic analysis of cardiorenal outcome trials in type 2 diabetes.
AIMS
Most trials leading to the approval of glucagon-like peptide receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) were primarily designed to confirm their non-inferiority to placebo (commonly using an upper 95% confidence limit threshold of 1.3) and, if confirmed, superiority (threshold 1): this asymmetry of margins (1 vs. 1.3) favours the active intervention. We aimed to quantify the probability of clinical superiority of the active treatment by applying the same threshold used to claim non-inferiority.
MATERIALS AND METHODS
We searched PubMed and Cochrane CENTRAL for cardiorenal outcome trials in subjects with type 2 diabetes published before 5 December 2021, to reconstruct from Kaplan-Meier plots individual-level data for the primary outcome or all-cause mortality. We calculated Bayesian posterior densities to obtain the probability for a treatment effect (hazard ratio) <0.769, which is symmetric to the 1.3 threshold (i.e. its reciprocal 1/1.3), emulating a scenario where the active treatment is placebo and placebo is the active treatment.
RESULTS
We extracted data from 27 Kaplan-Meier plots (18 for the primary outcome, nine for mortality). Probabilities of clinical superiority to placebo varied significantly: for GLP-1RAs, from a minimum of 0% to a maximum of 69% for the primary outcome and from 0% to 8% for mortality; corresponding estimates for SGLT2is were 0% to 96% and 0% to 93%. Probabilities were on average greater for SGLT2is, particularly in trials investigating kidney or heart failure outcomes.
CONCLUSIONS
The probability of clinical superiority to placebo varies widely across trials previously reported as showing superiority of GLP-1RAs or SGLT2is compared with placebo. These results showed within- and between-class differences, highlight the drawbacks of a binary interpretation of the results, particularly in the context of the current designs of non-inferiority trials, and have implications for decision makers and future clinical recommendations.
Topics: Bayes Theorem; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 35491523
DOI: 10.1111/dom.14735 -
Journal of Stroke and Cerebrovascular... Jun 2016Brain edema formation is a major cause of brain damages and the high mortality of ischemic stroke. The aim of this review is to explore the relationship between ischemic... (Review)
Review
BACKGROUND
Brain edema formation is a major cause of brain damages and the high mortality of ischemic stroke. The aim of this review is to explore the relationship between ischemic brain edema formation and vasopressin (VP) hypersecretion in addition to the oxygen and glucose deprivation and the ensuing reperfusion injury.
METHODS
Pertinent studies involving ischemic stroke, brain edema formation, astrocytes, and VP were identified by a search of the PubMed and the Web of Science databases in January 2016. Based on clinical findings and reports of animal experiments using ischemic stroke models, this systematic review reanalyzes the implication of individual reports in the edema formation and then establishes the inherent links among them.
RESULTS
This systematic review reveals that cytotoxic edema and vasogenic brain edema in classical view are mainly under the influence of a continuous malfunction of astrocytic plasticity. Adaptive VP secretion can modulate membrane ion transport, water permeability, and blood-brain barrier integrity, which are largely via changing astrocytic plasticity. Maladaptive VP hypersecretion leads to disruptions of ion and water balance across cell membranes as well as the integrity of the blood-brain barrier. This review highlights our current understandings of the cellular mechanisms underlying ischemic brain edema formation and its association with VP hypersecretion.
CONCLUSIONS
VP hypersecretion promotes brain edema formation in ischemic stroke by disrupting hydromineral balance in the neurovascular unit; suppressing VP hypersecretion has the potential to alleviate ischemic brain edema.
Topics: Animals; Astrocytes; Brain; Brain Edema; Brain Ischemia; Humans; Phenotype; Prognosis; Risk Factors; Signal Transduction; Stroke; Up-Regulation; Vasopressins
PubMed: 27068863
DOI: 10.1016/j.jstrokecerebrovasdis.2016.02.002